HIV-1 Latency pp 181-210 | Cite as

Immune Interventions to Eliminate the HIV Reservoir

  • Denise C. Hsu
  • Jintanat AnanworanichEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 417)


Inducing HIV remission is a monumental challenge. A potential strategy is the “kick and kill” approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV. Specific strategies include increasing the magnitude and breadth of T cell responses through therapeutic vaccinations, reversing the effects of T cell exhaustion using immune checkpoint inhibition, employing bispecific T cell targeting immunomodulatory proteins or dual-affinity re-targeting molecules to direct cytotoxic T lymphocytes to virus-expressing cells and broadly neutralizing antibody infusions. Methods to steer immune responses to tissue sites where latently infected cells are located need to be further explored. Ultimately, strategies to induce HIV remission must be tolerable, safe, and scalable in order to make a global impact.



This work was supported by a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. and the U.S. Department of the Army. The views expressed herein are those of the authors and should not be construed to represent the positions of the Departments of the Army or Defense. Trade names are used for identification purposes only and do not imply endorsement.


  1. Ahmed T, Borthwick NJ, Gilmour J, Hayes P, Dorrell L, Hanke T (2016) Control of HIV-1 replication in vitro by vaccine-induced human CD8(+) T cells through conserved subdominant Pol epitopes. Vaccine 34(9):1215–1224. doi:10.1016/j.vaccine.2015.12.021CrossRefPubMedPubMedCentralGoogle Scholar
  2. Altfeld M, Rosenberg ES, Shankarappa R, Mukherjee JS, Hecht FM, Eldridge RL, Addo MM, Poon SH, Phillips MN, Robbins GK, Sax PE, Boswell S, Kahn JO, Brander C, Goulder PJ, Levy JA, Mullins JI, Walker BD (2001) Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med 193(2):169–180CrossRefGoogle Scholar
  3. Amancha PK, Hong JJ, Rogers K, Ansari AA, Villinger F (2013) In vivo blockade of the programmed cell death-1 pathway using soluble recombinant PD-1-Fc enhances CD4+ and CD8+ T cell responses but has limited clinical benefit. J Immunol 191(12):6060–6070. doi:10.4049/jimmunol.1302044CrossRefPubMedGoogle Scholar
  4. Ananworanich J, Sacdalan CP, Pinyakorn S, Chomont N, de Souza M, Luekasemsuk T, Schuetz A, Krebs SJ, Dewar R, Jagodzinski L, Ubolyam S, Trichavaroj R, Tovanabutra S, Spudich S, Valcour V, Sereti I, Michael N, Robb M, Phanuphak P, Kim JH, Phanuphak N (2016a) Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection. J Virus Erad 2:43–48PubMedPubMedCentralGoogle Scholar
  5. Ananworanich J, Chomont N, Eller LA, Kroon E, Tovanabutra S, Bose M, Nau M, Fletcher JL, Tipsuk S, Vandergeeten C, O’Connell RJ, Pinyakorn S, Michael N, Phanuphak N, Robb ML, Rv, groups RSs (2016) HIV DNA set point is rapidly established in acute HIV infection and dramatically reduced by early ART. EBioMedicine 11:68–72. doi:10.1016/j.ebiom.2016.07.024CrossRefGoogle Scholar
  6. Angel JB, Routy JP, Tremblay C, Ayers D, Woods R, Singer J, Bernard N, Kovacs C, Smaill F, Gurunathan S, Sekaly RP (2011) A randomized controlled trial of HIV therapeutic vaccination using ALVAC with or without Remune. Aids 25(6):731–739. doi:10.1097/QAD.0b013e328344cea5CrossRefPubMedGoogle Scholar
  7. Archin NM, Vaidya NK, Kuruc JD, Liberty AL, Wiegand A, Kearney MF, Cohen MS, Coffin JM, Bosch RJ, Gay CL, Eron JJ, Margolis DM, Perelson AS (2012) Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci U S A 109(24):9523–9528. doi:10.1073/pnas.1120248109CrossRefPubMedPubMedCentralGoogle Scholar
  8. Arthos J, Cicala C, Martinelli E, Macleod K, Van Ryk D, Wei D, Xiao Z, Veenstra TD, Conrad TP, Lempicki RA, McLaughlin S, Pascuccio M, Gopaul R, McNally J, Cruz CC, Censoplano N, Chung E, Reitano KN, Kottilil S, Goode DJ, Fauci AS (2008) HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol 9(3):301–309. doi:10.1038/ni1566CrossRefPubMedGoogle Scholar
  9. Balazs AB, Chen J, Hong CM, Rao DS, Yang L, Baltimore D (2012) Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 481(7379):81–84. doi:10.1038/nature10660CrossRefGoogle Scholar
  10. Balazs AB, Ouyang Y, Hong CM, Chen J, Nguyen SM, Rao DS, An DS, Baltimore D (2014) Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med 20(3):296–300. doi:10.1038/nm.3471CrossRefPubMedPubMedCentralGoogle Scholar
  11. Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O’Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW (2016) Effect of HIV antibody VRC01 on viral rebound after treatment interruption. N Engl J Med 375(21):2037–2050. doi:10.1056/NEJMoa1608243CrossRefPubMedPubMedCentralGoogle Scholar
  12. Barouch DH, O’Brien KL, Simmons NL, King SL, Abbink P, Maxfield LF, Sun YH, La Porte A, Riggs AM, Lynch DM, Clark SL, Backus K, Perry JR, Seaman MS, Carville A, Mansfield KG, Szinger JJ, Fischer W, Muldoon M, Korber B (2010) Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med 16(3):319–323. doi:10.1038/nm.2089CrossRefPubMedPubMedCentralGoogle Scholar
  13. Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS, Dugast AS, Alter G, Ferguson M, Li W, Earl PL, Moss B, Giorgi EE, Szinger JJ, Eller LA, Billings EA, Rao M, Tovanabutra S, Sanders-Buell E, Weijtens M, Pau MG, Schuitemaker H, Robb ML, Kim JH, Korber BT, Michael NL (2013) Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell 155(3):531–539. doi:10.1016/j.cell.2013.09.061CrossRefPubMedGoogle Scholar
  14. Bell RD, Ehlers MD (2014) Breaching the blood-brain barrier for drug delivery. Neuron 81(1):1–3. doi:10.1016/j.neuron.2013.12.023CrossRefPubMedGoogle Scholar
  15. Bolton DL, Pegu A, Wang K, McGinnis K, Nason M, Foulds K, Letukas V, Schmidt SD, Chen X, Todd JP, Lifson JD, Rao S, Michael NL, Robb ML, Mascola JR, Koup RA (2015) Human immunodeficiency virus type 1 monoclonal antibodies suppress acute simian-human immunodeficiency virus viremia and limit seeding of cell-associated viral reservoirs. J Virol 90(3):1321–1332. doi:10.1128/JVI.02454-15CrossRefPubMedGoogle Scholar
  16. Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng’ang’a D, Nkolola JP, Brinkman AL, Peter L, Lee BC, Jimenez J, Jetton D, Mondesir J, Mojta S, Chandrashekar A, Molloy K, Alter G, Gerold JM, Hill AL, Lewis MG, Pau MG, Schuitemaker H, Hesselgesser J, Geleziunas R, Kim JH, Robb ML, Michael NL, Barouch DH (2016) Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540(7632):284–287. doi:10.1038/nature20583CrossRefPubMedPubMedCentralGoogle Scholar
  17. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68(9):6103–6110PubMedPubMedCentralGoogle Scholar
  18. Bournazos S, Gazumyan A, Seaman MS, Nussenzweig MC, Ravetch JV (2016) Bispecific anti-HIV-1 antibodies with enhanced breadth and potency. Cell 165(7):1609–1620. doi:10.1016/j.cell.2016.04.050CrossRefPubMedPubMedCentralGoogle Scholar
  19. Buzon MJ, Martin-Gayo E, Pereyra F, Ouyang Z, Sun H, Li JZ, Piovoso M, Shaw A, Dalmau J, Zangger N, Martinez-Picado J, Zurakowski R, Yu XG, Telenti A, Walker BD, Rosenberg ES, Lichterfeld M (2014) Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells. J Virol 88(17):10056–10065. doi:10.1128/JVI.01046-14CrossRefPubMedPubMedCentralGoogle Scholar
  20. Byrareddy SN, Arthos J, Cicala C, Villinger F, Ortiz KT, Little D, Sidell N, Kane MA, Yu J, Jones JW, Santangelo PJ, Zurla C, McKinnon LR, Arnold KB, Woody CE, Walter L, Roos C, Noll A, Van Ryk D, Jelicic K, Cimbro R, Gumber S, Reid MD, Adsay V, Amancha PK, Mayne AE, Parslow TG, Fauci AS, Ansari AA (2016) Sustained virologic control in SIV+ macaques after antiretroviral and alpha4beta7 antibody therapy. Science 354(6309):197–202. doi:10.1126/science.aag1276CrossRefPubMedPubMedCentralGoogle Scholar
  21. Calcagno A, Simiele M, Alberione MC, Bracchi M, Marinaro L, Ecclesia S, Di Perri G, D’Avolio A, Bonora S (2015) Cerebrospinal fluid inhibitory quotients of antiretroviral drugs in HIV-infected patients are associated with compartmental viral control. Clin Infect Dis 60(2):311–317. doi:10.1093/cid/ciu773CrossRefPubMedGoogle Scholar
  22. Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, Peytavin G, Tubiana R, Pialoux G, Katlama C (2010) Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis 50(5):773–778. doi:10.1086/650538CrossRefGoogle Scholar
  23. Carrington M, O’Brien SJ (2003) The influence of HLA genotype on AIDS. Annu Rev Med 54:535–551. doi:10.1146/ Scholar
  24. Cartwright EK, Spicer L, Smith SA, Lee D, Fast R, Paganini S, Lawson BO, Nega M, Easley K, Schmitz JE, Bosinger SE, Paiardini M, Chahroudi A, Vanderford TH, Estes JD, Lifson JD, Derdeyn CA, Silvestri G (2016) CD8(+) lymphocytes are required for maintaining viral suppression in siv-infected macaques treated with short-term antiretroviral therapy. Immunity 45(3):656–668. doi:10.1016/j.immuni.2016.08.018CrossRefPubMedPubMedCentralGoogle Scholar
  25. Casazza JP, Betts MR, Picker LJ, Koup RA (2001) Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. J Virol 75(14):6508–6516. doi:10.1128/JVI.75.14.6508-6516.2001CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chomont N, Perreau M (2016) Strategies for targeting residual HIV infection. Curr Opin HIV AIDS 11(4):359–361. doi:10.1097/COH.0000000000000291CrossRefPubMedPubMedCentralGoogle Scholar
  27. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP (2009) HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15(8):893–900. doi:10.1038/nm.1972CrossRefPubMedPubMedCentralGoogle Scholar
  28. Chun TW, Finzi D, Margolick J, Chadwick K, Schwartz D, Siliciano RF (1995) In vivo fate of HIV-1-infected T cells: quantitative analysis of the transition to stable latency. Nat Med 1(12):1284–1290CrossRefGoogle Scholar
  29. Chun TW, Carruth L, Finzi D, Shen X, DiGiuseppe JA, Taylor H, Hermankova M, Chadwick K, Margolick J, Quinn TC, Kuo YH, Brookmeyer R, Zeiger MA, Barditch-Crovo P, Siliciano RF (1997) Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387(6629):183–188. doi:10.1038/387183a0CrossRefPubMedGoogle Scholar
  30. Chun TW, Murray D, Justement JS, Blazkova J, Hallahan CW, Fankuchen O, Gittens K, Benko E, Kovacs C, Moir S, Fauci AS (2014) Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir. Proc Natl Acad Sci U S A 111(36):13151–13156. doi:10.1073/pnas.1414148111CrossRefPubMedPubMedCentralGoogle Scholar
  31. Cicala C, Martinelli E, McNally JP, Goode DJ, Gopaul R, Hiatt J, Jelicic K, Kottilil S, Macleod K, O’Shea A, Patel N, Van Ryk D, Wei D, Pascuccio M, Yi L, McKinnon L, Izulla P, Kimani J, Kaul R, Fauci AS, Arthos J (2009) The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A 106(49):20877–20882. doi:10.1073/pnas.0911796106CrossRefPubMedPubMedCentralGoogle Scholar
  32. Cillo AR, Mellors JW (2016) Which therapeutic strategy will achieve a cure for HIV-1? Curr Opin Virol 18:14–19. doi:10.1016/j.coviro.2016.02.001CrossRefPubMedGoogle Scholar
  33. Crowell TA, Colby DJ, Pinyakorn S, Intasan J, Benjapornpong K, Tanjnareel K et al (2017) HIV-specific broadly-neutralizing monoclonal antibody, VRC01, minimally impacts time to viral rebound following treatment interruption in virologically-suppressed, HIV-infected participants who initiated antiretroviral therapy during acute HIV infection. IAS 2017, ParisGoogle Scholar
  34. Connick E, Mattila T, Folkvord JM, Schlichtemeier R, Meditz AL, Ray MG, McCarter MD, Mawhinney S, Hage A, White C, Skinner PJ (2007) CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J Immunol 178(11):6975–6983CrossRefGoogle Scholar
  35. Connick E, Folkvord JM, Lind KT, Rakasz EG, Miles B, Wilson NA, Santiago ML, Schmitt K, Stephens EB, Kim HO, Wagstaff R, Li S, Abdelaal HM, Kemp N, Watkins DI, MaWhinney S, Skinner PJ (2014) Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL. J Immunol 193(11):5613–5625. doi:10.4049/jimmunol.1401161CrossRefPubMedPubMedCentralGoogle Scholar
  36. Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN (2007) Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 82(6):1365–1374. doi:10.1189/jlb.0307166CrossRefPubMedGoogle Scholar
  37. Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354(17):1813–1826. doi:10.1056/NEJMra052638CrossRefPubMedGoogle Scholar
  38. Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer Immunother Sci 342(6165):1432–1433. doi:10.1126/science.342.6165.1432CrossRefGoogle Scholar
  39. Dahabieh MS, Battivelli E, Verdin E (2015) Understanding HIV latency: the road to an HIV cure. Annu Rev Med 66:407–421. doi:10.1146/annurev-med-092112-152941CrossRefPubMedPubMedCentralGoogle Scholar
  40. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443(7109):350–354. doi:10.1038/nature05115CrossRefGoogle Scholar
  41. Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, Chomont N, Douek D, Lifson JD, Lo YR, Kuritzkes D, Margolis D, Mellors J, Persaud D, Tucker JD, Barre-Sinoussi F, International ASTaCWG, Alter G, Auerbach J, Autran B, Barouch DH, Behrens G, Cavazzana M, Chen Z, Cohen EA, Corbelli GM, Eholie S, Eyal N, Fidler S, Garcia L, Grossman C, Henderson G, Henrich TJ, Jefferys R, Kiem HP, McCune J, Moodley K, Newman PA, Nijhuis M, Nsubuga MS, Ott M, Palmer S, Richman D, Saez-Cirion A, Sharp M, Siliciano J, Silvestri G, Singh J, Spire B, Taylor J, Tolstrup M, Valente S, van Lunzen J, Walensky R, Wilson I, Zack J (2016) International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat Med. doi:10.1038/nm.4108CrossRefPubMedGoogle Scholar
  42. Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF (2015) Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517(7534):381–385. doi:10.1038/nature14053CrossRefPubMedPubMedCentralGoogle Scholar
  43. Doria-Rose NA, Klein RM, Manion MM, O’Dell S, Phogat A, Chakrabarti B, Hallahan CW, Migueles SA, Wrammert J, Ahmed R, Nason M, Wyatt RT, Mascola JR, Connors M (2009) Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol 83(1):188–199. doi:10.1128/JVI.01583-08CrossRefPubMedGoogle Scholar
  44. Erle DJ, Briskin MJ, Butcher EC, Garcia-Pardo A, Lazarovits AI, Tidswell M (1994) Expression and function of the MAdCAM-1 receptor, integrin alpha4beta7, on human leukocytes. J Immunol 153(2):517–528PubMedGoogle Scholar
  45. Eron JJ, Gay C, Bosch R, Ritz J, Hataye JM, Hwang C, Tressler RL, Mason SW, Koup RA, Mellors JW (2016) Safety, immunologic and virologic activity of anti-PD-L1 in HIV-1 participants on ART. Abstract 25. In: Conference on Retroviruses and Opportunistic Infections CROI, pp 22–25Google Scholar
  46. Euler Z, Alter G (2015) Exploring the potential of monoclonal antibody therapeutics for HIV-1 eradication. AIDS Res Hum Retroviruses 31(1):13–24. doi:10.1089/AID.2014.0235CrossRefPubMedPubMedCentralGoogle Scholar
  47. Farstad IN, Halstensen TS, Kvale D, Fausa O, Brandtzaeg P (1997) Topographic distribution of homing receptors on B and T cells in human gut-associated lymphoid tissue: relation of L-selectin and integrin alpha4beta7 to naive and memory phenotypes. Am J Pathol 150(1):187–199PubMedPubMedCentralGoogle Scholar
  48. Fidler S, Olson AD, Bucher HC, Fox J, Thornhill J, Morrison C, Muga R, Phillips A, Frater J, Porter K (2017) Virological blips and predictors of post treatment viral control after stopping ART started in primary HIV infection. J Acquir Immune Defic Syndr 74(2):126–133. doi:10.1097/QAI.0000000000001220CrossRefPubMedGoogle Scholar
  49. Fischer W, Perkins S, Theiler J, Bhattacharya T, Yusim K, Funkhouser R, Kuiken C, Haynes B, Letvin NL, Walker BD, Hahn BH, Korber BT (2007) Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med 13(1):100–106. doi:10.1038/nm1461CrossRefPubMedGoogle Scholar
  50. Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, Anderson J, Perkey K, Stevenson M, Perelson AS, Douek DC, Haase AT, Schacker TW (2014) Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111(6):2307–2312. doi:10.1073/pnas.1318249111CrossRefPubMedPubMedCentralGoogle Scholar
  51. Forthal D, Hope TJ, Alter G (2013) New paradigms for functional HIV-specific nonneutralizing antibodies. Curr Opin HIV AIDS 8(5):393–401. doi:10.1097/COH.0b013e328363d486CrossRefPubMedPubMedCentralGoogle Scholar
  52. Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak M Jr, Estes JD, Lifson JD, Picker LJ (2015) B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med 21(2):132–139. doi:10.1038/nm.3781CrossRefPubMedPubMedCentralGoogle Scholar
  53. Gandhi RT, O’Neill D, Bosch RJ, Chan ES, Bucy RP, Shopis J, Baglyos L, Adams E, Fox L, Purdue L, Marshak A, Flynn T, Masih R, Schock B, Mildvan D, Schlesinger SJ, Marovich MA, Bhardwaj N, Jacobson JM, team ACTGA (2009) A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy. Vaccine 27(43):60886094. doi:10.1016/j.vaccine.2009.05.016CrossRefGoogle Scholar
  54. Garcia F, Lejeune M, Climent N, Gil C, Alcami J, Morente V, Alos L, Ruiz A, Setoain J, Fumero E, Castro P, Lopez A, Cruceta A, Piera C, Florence E, Pereira A, Libois A, Gonzalez N, Guila M, Caballero M, Lomena F, Joseph J, Miro JM, Pumarola T, Plana M, Gatell JM, Gallart T (2005) Therapeutic immunization with dendritic cells loaded with heat-inactivated autologous HIV-1 in patients with chronic HIV-1 infection. J Infect Dis 191(10):1680–1685. doi:10.1086/429340CrossRefPubMedGoogle Scholar
  55. Garcia F, Leon A, Gatell JM, Plana M, Gallart T (2012) Therapeutic vaccines against HIV infection. Hum Vaccin Immunother 8(5):569–581. doi:10.4161/hv.19555CrossRefPubMedGoogle Scholar
  56. Garcia F, Climent N, Guardo AC, Gil C, Leon A, Autran B, Lifson JD, Martinez-Picado J, Dalmau J, Clotet B, Gatell JM, Plana M, Gallart T, Group DMOS (2013a) A dendritic cell-based vaccine elicits T cell responses associated with control of HIV-1 replication. Sci Transl Med 5(166):166ra162. doi:10.1126/scitranslmed.3004682CrossRefGoogle Scholar
  57. Garcia F, Plana M, Climent N, Leon A, Gatell JM, Gallart T (2013b) Dendritic cell based vaccines for HIV infection: the way ahead. Hum Vaccin Immunother 9(11):2445–2452CrossRefGoogle Scholar
  58. Gautam R, Nishimura Y, Pegu A, Nason MC, Klein F, Gazumyan A, Golijanin J, Buckler-White A, Sadjadpour R, Wang K, Mankoff Z, Schmidt SD, Lifson JD, Mascola JR, Nussenzweig MC, Martin MA (2016) A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature 533(7601):105–109. doi:10.1038/nature17677CrossRefPubMedPubMedCentralGoogle Scholar
  59. Goldstein G, Damiano E, Donikyan M, Pasha M, Beckwith E, Chicca J (2012) HIV-1 Tat B-cell epitope vaccination was ineffectual in preventing viral rebound after ART cessation: HIV rebound with current ART appears to be due to infection with new endogenous founder virus and not to resurgence of pre-existing Tat-dependent viremia. Hum Vaccine Immunother 8(10):1425–1430. doi:10.4161/hv.21616CrossRefGoogle Scholar
  60. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB (2010) Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363(22):2091–2101. doi:10.1056/NEJMoa1004383CrossRefPubMedPubMedCentralGoogle Scholar
  61. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, CCC B, Letvin N, Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206(6):1253–1272. doi:10.1084/jem.20090365CrossRefPubMedPubMedCentralGoogle Scholar
  62. Goujard C, Girault I, Rouzioux C, Lecuroux C, Deveau C, Chaix ML, Jacomet C, Talamali A, Delfraissy JF, Venet A, Meyer L, Sinet M, Group ACPS (2012) HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy. Antivir Ther 17(6):1001–1009. doi:10.3851/IMP2273CrossRefGoogle Scholar
  63. Granich R, Gupta S, Montaner J, Williams B, Zuniga JM (2016) Pattern, determinants, and impact of HIV spending on care and treatment in 38 high-burden low- and middle-income countries. J Int Assoc Provid AIDS Care 15(2):91–100. doi:10.1177/2325957415623261CrossRefPubMedGoogle Scholar
  64. Gray ES, Madiga MC, Hermanus T, Moore PL, Wibmer CK, Tumba NL, Werner L, Mlisana K, Sibeko S, Williamson C, Abdool Karim SS, Morris L, Team CS (2011) The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J Virol 85(10):4828–4840. doi:10.1128/JVI.00198-11CrossRefPubMedPubMedCentralGoogle Scholar
  65. Hancock G, Yang H, Yorke E, Wainwright E, Bourne V, Frisbee A, Payne TL, Berrong M, Ferrari G, Chopera D, Hanke T, Mothe B, Brander C, McElrath MJ, McMichael A, Goonetilleke N, Tomaras GD, Frahm N, Dorrell L (2015) Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses. PLoS Pathog 11(2):e1004658. doi:10.1371/journal.ppat.1004658CrossRefPubMedPubMedCentralGoogle Scholar
  66. Hanke T (2014) Conserved immunogens in prime-boost strategies for the next-generation HIV-1 vaccines. Expert Opin Biol Ther 14(5):601–616. doi:10.1517/14712598.2014.885946CrossRefPubMedGoogle Scholar
  67. He R, Hou S, Liu C, Zhang A, Bai Q, Han M, Yang Y, Wei G, Shen T, Yang X, Xu L, Chen X, Hao Y, Wang P, Zhu C, Ou J, Liang H, Ni T, Zhang X, Zhou X, Deng K, Chen Y, Luo Y, Xu J, Qi H, Wu Y, Ye L (2016) Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection. Nature 537(7620):412–428. doi:10.1038/nature19317CrossRefPubMedGoogle Scholar
  68. Hertz T, Ahmed H, Friedrich DP, Casimiro DR, Self SG, Corey L, McElrath MJ, Buchbinder S, Horton H, Frahm N, Robertson MN, Graham BS, Gilbert P (2013) HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1. PLoS Pathog 9(6):e1003404. doi:10.1371/journal.ppat.1003404CrossRefPubMedPubMedCentralGoogle Scholar
  69. Hessell AJ, Jaworski JP, Epson E, Matsuda K, Pandey S, Kahl C, Reed J, Sutton WF, Hammond KB, Cheever TA, Barnette PT, Legasse AW, Planer S, Stanton JJ, Pegu A, Chen X, Wang K, Siess D, Burke D, Park BS, Axthelm MK, Lewis A, Hirsch VM, Graham BS, Mascola JR, Sacha JB, Haigwood NL (2016) Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nat Med 22(4):362–368. doi:10.1038/nm.4063CrossRefPubMedPubMedCentralGoogle Scholar
  70. Hill AL, Rosenbloom DI, Fu F, Nowak MA, Siliciano RF (2014) Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1. Proc Natl Acad Sci U S A 111(37):13475–13480. doi:10.1073/pnas.1406663111CrossRefPubMedPubMedCentralGoogle Scholar
  71. Hoffmann M, Pantazis N, Martin GE, Hickling S, Hurst J, Meyerowitz J, Willberg CB, Robinson N, Brown H, Fisher M, Kinloch S, Babiker A, Weber J, Nwokolo N, Fox J, Fidler S, Phillips R, Frater J, Spartac Investigators C (2016) Exhaustion of activated CD8 T cells predicts disease progression in primary HIV-1 infection. PLoS Pathog 12(7):e1005661. doi:10.1371/journal.ppat.1005661CrossRefPubMedPubMedCentralGoogle Scholar
  72. Hraber P, Seaman MS, Bailer RT, Mascola JR, Montefiori DC, Korber BT (2014) Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS 28(2):163–169. doi:10.1097/QAD.0000000000000106CrossRefPubMedPubMedCentralGoogle Scholar
  73. Hryniewicz A, Boasso A, Edghill-Smith Y, Vaccari M, Fuchs D, Venzon D, Nacsa J, Betts MR, Tsai WP, Heraud JM, Beer B, Blanset D, Chougnet C, Lowy I, Shearer GM, Franchini G (2006) CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques. Blood 108(12):3834–3842. doi:10.1182/blood-2006-04-010637CrossRefPubMedPubMedCentralGoogle Scholar
  74. Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann WK, Thiel E (2009) Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 360(7):692–698. doi:10.1056/NEJMoa0802905CrossRefPubMedGoogle Scholar
  75. Ide F, Nakamura T, Tomizawa M, Kawana-Tachikawa A, Odawara T, Hosoya N, Iwamoto A (2006) Peptide-loaded dendritic-cell vaccination followed by treatment interruption for chronic HIV-1 infection: a phase 1 trial. J Med Virol 78(6):711–718. doi:10.1002/jmv.20612CrossRefPubMedGoogle Scholar
  76. Jacobson JM, Pat Bucy R, Spritzler J, Saag MS, Eron JJ, Jr., Coombs RW, Wang R, Fox L, Johnson VA, Cu-Uvin S, Cohn SE, Mildvan D, O’Neill D, Janik J, Purdue L, O’Connor DK, Vita CD, Frank I, National Institute of A, Infectious Diseases ACTGPT (2006) Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP1452, promotes host control of HIV replication: the results of AIDS Clinical Trials Group 5068. J Infect Dis 194(5):623–632. doi:10.1086/506364
  77. Jacobson JM, Routy JP, Welles S, DeBenedette M, Tcherepanova I, Angel JB, Asmuth DM, Stein DK, Baril JG, McKellar M, Margolis DM, Trottier B, Wood K, Nicolette C (2016) Dendritic cell immunotherapy for HIV-1 infection using autologous HIV-1 RNA: a randomized, double-blind, placebo-controlled clinical trial. J Acquir Immune Defic Syndr 72(1):31–38. doi:10.1097/QAI.0000000000000926CrossRefPubMedPubMedCentralGoogle Scholar
  78. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Blanchard J, Irwin CE, Safrit JT, Mittler J, Weinberger L, Kostrikis LG, Zhang L, Perelson AS, Ho DD (1999) Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189(6):991–998CrossRefGoogle Scholar
  79. Johnson PR, Schnepp BC, Zhang J, Connell MJ, Greene SM, Yuste E, Desrosiers RC, Clark KR (2009) Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys. Nat Med 15(8):901–906. doi:10.1038/nm.1967CrossRefPubMedPubMedCentralGoogle Scholar
  80. Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ (2016a) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375(18):1749–1755. doi:10.1056/NEJMoa1609214CrossRefPubMedPubMedCentralGoogle Scholar
  81. Johnson DB, Sullivan RJ, Ott PA, Carlino MS, Khushalani NI, Ye F, Guminski A, Puzanov I, Lawrence DP, Buchbinder EI, Mudigonda T, Spencer K, Bender C, Lee J, Kaufman HL, Menzies AM, Hassel JC, Mehnert JM, Sosman JA, Long GV, Clark JI (2016b) Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol 2(2):234–240. doi:10.1001/jamaoncol.2015.4368CrossRefPubMedGoogle Scholar
  82. Jones RB, Walker BD (2016) HIV-specific CD8(+) T cells and HIV eradication. J Clin Invest 126(2):455–463. doi:10.1172/JCI80566CrossRefPubMedPubMedCentralGoogle Scholar
  83. Kader M, Wang X, Piatak M, Lifson J, Roederer M, Veazey R, Mattapallil JJ (2009) Alpha4(+) beta7(hi) CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol 2(5):439–449. doi:10.1038/mi.2009.90CrossRefPubMedPubMedCentralGoogle Scholar
  84. Kassu A, Marcus RA, D’Souza MB, Kelly-McKnight EA, Golden-Mason L, Akkina R, Fontenot AP, Wilson CC, Palmer BE (2010) Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection. J Immunol 185(5):3007–3018. doi:10.4049/jimmunol.1000156CrossRefPubMedPubMedCentralGoogle Scholar
  85. Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, Palmer S, Brockman M, Rathod A, Piechocka-Trocha A, Baker B, Zhu B, Le Gall S, Waring MT, Ahern R, Moss K, Kelleher AD, Coffin JM, Freeman GJ, Rosenberg ES, Walker BD (2007) Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 8(11):1246–1254. doi:10.1038/ni1515CrossRefPubMedGoogle Scholar
  86. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 105(21):7552–7557. doi:10.1073/pnas.0802203105CrossRefPubMedPubMedCentralGoogle Scholar
  87. Kinloch-de Loes S, Hoen B, Smith DE, Autran B, Lampe FC, Phillips AN, Goh LE, Andersson J, Tsoukas C, Sonnerborg A, Tambussi G, Girard PM, Bloch M, Battegay M, Carter N, El Habib R, Theofan G, Cooper DA, Perrin L, Group QS (2005) Impact of therapeutic immunization on HIV-1 viremia after discontinuation of antiretroviral therapy initiated during acute infection. J Infect Dis 192(4):607–617. doi:10.1086/432002CrossRefGoogle Scholar
  88. Klein MR, van Baalen CA, Holwerda AM, Kerkhof Garde SR, Bende RJ, Keet IP, Eeftinck-Schattenkerk JK, Osterhaus AD, Schuitemaker H, Miedema F (1995) Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J Exp Med 181(4):1365–1372CrossRefGoogle Scholar
  89. Ko SY, Pegu A, Rudicell RS, Yang ZY, Joyce MG, Chen X, Wang K, Bao S, Kraemer TD, Rath T, Zeng M, Schmidt SD, Todd JP, Penzak SR, Saunders KO, Nason MC, Haase AT, Rao SS, Blumberg RS, Mascola JR, Nabel GJ (2014) Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature 514(7524):642–645. doi:10.1038/nature13612CrossRefPubMedPubMedCentralGoogle Scholar
  90. Kong R, Louder MK, Wagh K, Bailer RT, deCamp A, Greene K, Gao H, Taft JD, Gazumyan A, Liu C, Nussenzweig MC, Korber B, Montefiori DC, Mascola JR (2015) Improving neutralization potency and breadth by combining broadly reactive HIV-1 antibodies targeting major neutralization epitopes. J Virol 89(5):2659–2671. doi:10.1128/JVI.03136-14CrossRefPubMedGoogle Scholar
  91. Kumar AM, Borodowsky I, Fernandez B, Gonzalez L, Kumar M (2007) Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol 13(3):210–224. doi:10.1080/13550280701327038CrossRefPubMedGoogle Scholar
  92. Kwong PD, Mascola JR, Nabel GJ (2013) Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nat Rev Immunol 13(9):693–701. doi:10.1038/nri3516CrossRefPubMedGoogle Scholar
  93. Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, Ramos A, Bian CB, Simek M, Allen S, Karita E, Kilembe W, Lakhi S, Inambao M, Kamali A, Sanders EJ, Anzala O, Edward V, Bekker LG, Tang J, Gilmour J, Kosakovsky-Pond SL, Phung P, Wrin T, Crotty S, Godzik A, Poignard P (2016) Broadly neutralizing antibody responses in a large longitudinal sub-saharan HIV primary infection cohort. PLoS Pathog 12(1):e1005369. doi:10.1371/journal.ppat.1005369CrossRefPubMedPubMedCentralGoogle Scholar
  94. Langford D, Marquie-Beck J, de Almeida S, Lazzaretto D, Letendre S, Grant I, McCutchan JA, Masliah E, Ellis RJ (2006) Relationship of antiretroviral treatment to postmortem brain tissue viral load in human immunodeficiency virus-infected patients. J Neurovirol 12(2):100–107. doi:10.1080/13550280600713932CrossRefPubMedGoogle Scholar
  95. Lazar GA, Dang W, Karki S, Vafa O, Peng JS, Hyun L, Chan C, Chung HS, Eivazi A, Yoder SC, Vielmetter J, Carmichael DF, Hayes RJ, Dahiyat BI (2006) Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci U S A 103(11):4005–4010. doi:10.1073/pnas.0508123103CrossRefPubMedPubMedCentralGoogle Scholar
  96. Lecuroux C, Girault I, Boutboul F, Urrutia A, Goujard C, Meyer L, Lambotte O, Chaix ML, Martinez V, Autran B, Sinet M, Venet A, Anrs Primo Cohort AHICSG, Cohort AA, Group AHS (2009a) Antiretroviral therapy initiation during primary HIV infection enhances both CD127 expression and the proliferative capacity of HIV-specific CD8+ T cells. Aids 23(13):1649–1658. doi:10.1097/QAD.0b013e32832e6634CrossRefGoogle Scholar
  97. Lecuroux C, Girault I, Urrutia A, Doisne JM, Deveau C, Goujard C, Meyer L, Sinet M, Venet A (2009b) Identification of a particular HIV-specific CD8+ T-cell subset with a CD27+ CD45RO-/RA+ phenotype and memory characteristics after initiation of HAART during acute primary HIV infection. Blood 113(14):3209–3217. doi:10.1182/blood-2008-07-167601CrossRefPubMedGoogle Scholar
  98. Leong YA, Chen Y, Ong HS, Wu D, Man K, Deleage C, Minnich M, Meckiff BJ, Wei Y, Hou Z, Zotos D, Fenix KA, Atnerkar A, Preston S, Chipman JG, Beilman GJ, Allison CC, Sun L, Wang P, Xu J, Toe JG, Lu HK, Tao Y, Palendira U, Dent AL, Landay AL, Pellegrini M, Comerford I, McColl SR, Schacker TW, Long HM, Estes JD, Busslinger M, Belz GT, Lewin SR, Kallies A, Yu D (2016) CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat Immunol 17(10):1187–1196. doi:10.1038/ni.3543CrossRefPubMedGoogle Scholar
  99. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ, Group C (2008) Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65(1):65–70. doi:10.1001/archneurol.2007.31CrossRefGoogle Scholar
  100. Letourneau S, Im EJ, Mashishi T, Brereton C, Bridgeman A, Yang H, Dorrell L, Dong T, Korber B, McMichael AJ, Hanke T (2007) Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS ONE 2(10):e984. doi:10.1371/journal.pone.0000984CrossRefPubMedPubMedCentralGoogle Scholar
  101. Levy Y, Thiebaut R, Montes M, Lacabaratz C, Sloan L, King B, Perusat S, Harrod C, Cobb A, Roberts LK, Surenaud M, Boucherie C, Zurawski S, Delaugerre C, Richert L, Chene G, Banchereau J, Palucka K (2014) Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load. Eur J Immunol 44(9):2802–2810. doi:10.1002/eji.201344433CrossRefPubMedGoogle Scholar
  102. Li JZ, Etemad B, Ahmed H, Aga E, Bosch RJ, Mellors JW, Kuritzkes DR, Lederman MM, Para M, Gandhi RT (2016) The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. Aids 30(3):343–353. doi:10.1097/QAD.0000000000000953CrossRefPubMedPubMedCentralGoogle Scholar
  103. Liu MK, Hawkins N, Ritchie AJ, Ganusov VV, Whale V, Brackenridge S, Li H, Pavlicek JW, Cai F, Rose-Abrahams M, Treurnicht F, Hraber P, Riou C, Gray C, Ferrari G, Tanner R, Ping LH, Anderson JA, Swanstrom R, B CC, Cohen M, Karim SS, Haynes B, Borrow P, Perelson AS, Shaw GM, Hahn BH, Williamson C, Korber BT, Gao F, Self S, McMichael A, Goonetilleke N (2013) Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest 123(1):380–393. doi:10.1172/JCI65330
  104. Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Kosakovsky Pond SL, Chung YS, Penugonda S, Chipman JG, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM (2016) Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 530(7588):51–56. doi:10.1038/nature16933CrossRefPubMedPubMedCentralGoogle Scholar
  105. Loret EP, Darque A, Jouve E, Loret EA, Nicolino-Brunet C, Morange S, Castanier E, Casanova J, Caloustian C, Bornet C, Coussirou J, Boussetta J, Couallier V, Blin O, Dussol B, Ravaux I (2016) Intradermal injection of a Tat Oyi-based therapeutic HIV vaccine reduces of 1.5 log copies/mL the HIV RNA rebound median and no HIV DNA rebound following cART interruption in a phase I/II randomized controlled clinical trial. Retrovirology 13:21. doi:10.1186/s12977-016-0251-3CrossRefPubMedPubMedCentralGoogle Scholar
  106. Lu CL, Murakowski DK, Bournazos S, Schoofs T, Sarkar D, Halper-Stromberg A, Horwitz JA, Nogueira L, Golijanin J, Gazumyan A, Ravetch JV, Caskey M, Chakraborty AK, Nussenzweig MC (2016) Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352(6288):1001–1004. doi:10.1126/science.aaf1279CrossRefPubMedPubMedCentralGoogle Scholar
  107. Macatangay BJ, Riddler SA, Wheeler ND, Spindler J, Lawani M, Hong F, Buffo MJ, Whiteside TL, Kearney MF, Mellors JW, Rinaldo CR (2016) Therapeutic vaccination with dendritic cells loaded with autologous HIV type 1-infected apoptotic cells. J Infect Dis 213(9):1400–1409. doi:10.1093/infdis/jiv582CrossRefPubMedGoogle Scholar
  108. Mellor AL, Munn DH (2004) IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4(10):762–774. doi:10.1038/nri1457CrossRefGoogle Scholar
  109. Menzies AM, Johnson DB, Ramanujam S, Atkinson VG, Wong AN, Park JJ, McQuade JL, Shoushtari AN, Tsai KK, Eroglu Z, Klein O, Hassel JC, Sosman JA, Guminski A, Sullivan RJ, Ribas A, Carlino MS, Davies MA, Sandhu SK, Long GV (2016) Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. doi:10.1093/annonc/mdw443CrossRefGoogle Scholar
  110. Merad M, Sathe P, Helft J, Miller J, Mortha A (2013) The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31:563–604. doi:10.1146/annurev-immunol-020711-074950CrossRefPubMedGoogle Scholar
  111. Migueles SA, Connors M (2015) Success and failure of the cellular immune response against HIV-1. Nat Immunol 16(6):563–570. doi:10.1038/ni.3161CrossRefPubMedGoogle Scholar
  112. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Martino L, Hallahan CW, Selig SM, Schwartz D, Sullivan J, Connors M (2000) HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci U S A 97(6):2709–2714. doi:10.1073/pnas.050567397CrossRefPubMedPubMedCentralGoogle Scholar
  113. Migueles SA, Weeks KA, Nou E, Berkley AM, Rood JE, Osborne CM, Hallahan CW, Cogliano-Shutta NA, Metcalf JA, McLaughlin M, Kwan R, Mican JM, Davey RT Jr, Connors M (2009) Defective human immunodeficiency virus-specific CD8+ T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J Virol 83(22):11876–11889. doi:10.1128/JVI.01153-09CrossRefPubMedPubMedCentralGoogle Scholar
  114. Mildner A, Jung S (2014) Development and function of dendritic cell subsets. Immunity 40(5):642–656. doi:10.1016/j.immuni.2014.04.016CrossRefPubMedGoogle Scholar
  115. Miller E, Bhardwaj N (2013) Dendritic cell dysregulation during HIV-1 infection. Immunol Rev 254(1):170–189. doi:10.1111/imr.12082CrossRefPubMedPubMedCentralGoogle Scholar
  116. Moore GL, Chen H, Karki S, Lazar GA (2010) Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2(2):181–189CrossRefGoogle Scholar
  117. Mothe B, Moltó J, Manzardo C, Coll J, Puertas MC, Martinez-Picado J, Hanke T, Clotet B, Brander C (2017) Viral control induced by HIVconsv vaccines & romidepsin in early treated individuals. Paper presented at the CROI, SeattleGoogle Scholar
  118. Mylvaganam GH, Silvestri G, Amara RR (2015) HIV therapeutic vaccines: moving towards a functional cure. Curr Opin Immunol 35:1–8. doi:10.1016/j.coi.2015.05.001CrossRefPubMedPubMedCentralGoogle Scholar
  119. Ndhlovu ZM, Kamya P, Mewalal N, Kloverpris HN, Nkosi T, Pretorius K, Laher F, Ogunshola F, Chopera D, Shekhar K, Ghebremichael M, Ismail N, Moodley A, Malik A, Leslie A, Goulder PJ, Buus S, Chakraborty A, Dong K, Ndung’u T, Walker BD (2015) Magnitude and kinetics of CD8+ T cell activation during hyperacute HIV infection impact viral set point. Immunity 43(3):591–604. doi:10.1016/j.immuni.2015.08.012CrossRefPubMedPubMedCentralGoogle Scholar
  120. Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11(12):823–836. doi:10.1038/nri3084CrossRefPubMedGoogle Scholar
  121. Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA (2017) Early antibody therapy can induce long-lasting immunity to SHIV. Nature 543(7646):559–563. doi:10.1038/nature21435CrossRefPubMedPubMedCentralGoogle Scholar
  122. Ogg GS, Jin X, Bonhoeffer S, Moss P, Nowak MA, Monard S, Segal JP, Cao Y, Rowland-Jones SL, Hurley A, Markowitz M, Ho DD, McMichael AJ, Nixon DF (1999) Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy. J Virol 73(1):797–800PubMedPubMedCentralGoogle Scholar
  123. Pantaleo G, Levy Y (2016) Therapeutic vaccines and immunological intervention in HIV infection: a paradigm change. Curr Opin HIV AIDS 11(6):576–584. doi:10.1097/COH.0000000000000324CrossRefPubMedGoogle Scholar
  124. Pardridge WM (2015) Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody. Expert Opin Drug Deliv 12(2):207–222. doi:10.1517/17425247.2014.952627CrossRefPubMedGoogle Scholar
  125. Pegu A, Asokan M, Wu L, Wang K, Hataye J, Casazza JP, Guo X, Shi W, Georgiev I, Zhou T, Chen X, O’Dell S, Todd JP, Kwong PD, Rao SS, Yang ZY, Koup RA, Mascola JR, Nabel GJ (2015) Activation and lysis of human CD4 cells latently infected with HIV-1. Nat Commun 6:8447. doi:10.1038/ncomms9447CrossRefPubMedPubMedCentralGoogle Scholar
  126. Peluso MJ, Ferretti F, Peterson J, Lee E, Fuchs D, Boschini A, Gisslen M, Angoff N, Price RW, Cinque P, Spudich S (2012) Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. Aids 26(14):1765–1774. doi:10.1097/QAD.0b013e328355e6b2CrossRefPubMedGoogle Scholar
  127. Peretz Y, He Z, Shi Y, Yassine-Diab B, Goulet JP, Bordi R, Filali-Mouhim A, Loubert JB, El-Far M, Dupuy FP, Boulassel MR, Tremblay C, Routy JP, Bernard N, Balderas R, Haddad EK, Sekaly RP (2012) CD160 and PD-1 co-expression on HIV-specific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog 8(8):e1002840. doi:10.1371/journal.ppat.1002840CrossRefPubMedPubMedCentralGoogle Scholar
  128. Petrovas C, Ferrando-Martinez S, Gerner MY, Casazza JP, Pegu A, Deleage C, Cooper A, Hataye J, Andrews S, Ambrozak D, Del Rio Estrada PM, Boritz E, Paris R, Moysi E, Boswell KL, Ruiz-Mateos E, Vagios I, Leal M, Ablanedo-Terrazas Y, Rivero A, Gonzalez-Hernandez LA, McDermott AB, Moir S, Reyes-Teran G, Docobo F, Pantaleo G, Douek DC, Betts MR, Estes JD, Germain RN, Mascola JR, Koup RA (2017) Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci Transl Med 9(373). doi:10.1126/scitranslmed.aag2285CrossRefGoogle Scholar
  129. Pollard RB, Rockstroh JK, Pantaleo G, Asmuth DM, Peters B, Lazzarin A, Garcia F, Ellefsen K, Podzamczer D, van Lunzen J, Arasteh K, Schurmann D, Clotet B, Hardy WD, Mitsuyasu R, Moyle G, Plettenberg A, Fisher M, Fatkenheuer G, Fischl M, Taiwo B, Baksaas I, Jolliffe D, Persson S, Jelmert O, Hovden AO, Sommerfelt MA, Wendel-Hansen V, Sorensen B (2014) Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis 14(4):291–300. doi:10.1016/S1473-3099(13)70343-8CrossRefPubMedGoogle Scholar
  130. Quigley MF, Gonzalez VD, Granath A, Andersson J, Sandberg JK (2007) CXCR5+ CCR7–CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles. Eur J Immunol 37(12):3352–3362. doi:10.1002/eji.200636746CrossRefPubMedGoogle Scholar
  131. Rasmussen TA, Lewin SR (2016) Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents? Curr Opin HIV AIDS 11(4):394–401. doi:10.1097/COH.0000000000000279CrossRefPubMedGoogle Scholar
  132. Richards JO, Karki S, Lazar GA, Chen H, Dang W, Desjarlais JR (2008) Optimization of antibody binding to FcgammaRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7(8):2517–2527. doi:10.1158/1535-7163.MCT-08-0201CrossRefPubMedGoogle Scholar
  133. Richman DD, Wrin T, Little SJ, Petropoulos CJ (2003) Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A 100(7):4144–4149. doi:10.1073/pnas.0630530100CrossRefPubMedPubMedCentralGoogle Scholar
  134. Riddler S, Durand C, Zheng L, Ritz J, Koup RA, Ledgerwood J, Macatangay B, Cyktor JC, Mellors JW (2017) VRC01 Infusion has no effect on HIV-1 persistance in ART-suppressed chronic infection. In: Conference on Retroviruses and Opportunistic InfectionsGoogle Scholar
  135. Rolland M, Nickle DC, Mullins JI (2007) HIV-1 group M conserved elements vaccine. PLoS Pathog 3(11):e157. doi:10.1371/journal.ppat.0030157CrossRefPubMedPubMedCentralGoogle Scholar
  136. Sadanand S, Suscovich TJ, Alter G (2016) Broadly neutralizing antibodies against HIV: new insights to inform vaccine design. Annu Rev Med 67:185–200. doi:10.1146/annurev-med-091014-090749CrossRefPubMedGoogle Scholar
  137. Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, Potard V, Versmisse P, Melard A, Prazuck T, Descours B, Guergnon J, Viard JP, Boufassa F, Lambotte O, Goujard C, Meyer L, Costagliola D, Venet A, Pancino G, Autran B, Rouzioux C, Group AVS (2013) Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 9(3):e1003211. doi:10.1371/journal.ppat.1003211CrossRefGoogle Scholar
  138. Sather DN, Armann J, Ching LK, Mavrantoni A, Sellhorn G, Caldwell Z, Yu X, Wood B, Self S, Kalams S, Stamatatos L (2009) Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 83(2):757–769. doi:10.1128/JVI.02036-08CrossRefPubMedGoogle Scholar
  139. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B (2000) CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192(11):1553–1562CrossRefGoogle Scholar
  140. Scheid JF, Horwitz JA, Bar-On Y, Kreider EF, Lu CL, Lorenzi JC, Feldmann A, Braunschweig M, Nogueira L, Oliveira T, Shimeliovich I, Patel R, Burke L, Cohen YZ, Hadrigan S, Settler A, Witmer-Pack M, West AP Jr, Juelg B, Keler T, Hawthorne T, Zingman B, Gulick RM, Pfeifer N, Learn GH, Seaman MS, Bjorkman PJ, Klein F, Schlesinger SJ, Walker BD, Hahn BH, Nussenzweig MC (2016) HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature 535(7613):556–560. doi:10.1038/nature18929CrossRefPubMedPubMedCentralGoogle Scholar
  141. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283(5403):857–860CrossRefGoogle Scholar
  142. Schnepp BC, Johnson PR (2014) Adeno-associated virus delivery of broadly neutralizing antibodies. Curr Opin HIV AIDS 9(3):250–256. doi:10.1097/COH.0000000000000056CrossRefPubMedPubMedCentralGoogle Scholar
  143. Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP Jr, Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, Nussenzweig MC (2016) HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science 352(6288):997–1001. doi:10.1126/science.aaf0972CrossRefPubMedPubMedCentralGoogle Scholar
  144. Schooley RT, Spritzler J, Wang H, Lederman MM, Havlir D, Kuritzkes DR, Pollard R, Battaglia C, Robertson M, Mehrotra D, Casimiro D, Cox K, Schock B, Team ACTGS (2010) AIDS clinical trials group 5197: a placebo-controlled trial of immunization of HIV-1-infected persons with a replication-deficient adenovirus type 5 vaccine expressing the HIV-1 core protein. J Infect Dis 202(5):705–716. doi:10.1086/655468CrossRefPubMedPubMedCentralGoogle Scholar
  145. Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF (2012) Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36(3):491–501. doi:10.1016/j.immuni.2012.01.014CrossRefPubMedPubMedCentralGoogle Scholar
  146. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9(6):727–728. doi:10.1038/nm880CrossRefPubMedPubMedCentralGoogle Scholar
  147. Simek MD, Rida W, Priddy FH, Pung P, Carrow E, Laufer DS, Lehrman JK, Boaz M, Tarragona-Fiol T, Miiro G, Birungi J, Pozniak A, McPhee DA, Manigart O, Karita E, Inwoley A, Jaoko W, Dehovitz J, Bekker LG, Pitisuttithum P, Paris R, Walker LM, Poignard P, Wrin T, Fast PE, Burton DR, Koff WC (2009) Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol 83(14):7337–7348. doi:10.1128/JVI.00110-09CrossRefPubMedPubMedCentralGoogle Scholar
  148. Sloan DD, Lam CY, Irrinki A, Liu L, Tsai A, Pace CS, Kaur J, Murry JP, Balakrishnan M, Moore PA, Johnson S, Nordstrom JL, Cihlar T, Koenig S (2015) Targeting HIV reservoir in infected CD4 T cells by dual-affinity re-targeting molecules (DARTs) that bind HIV envelope and recruit cytotoxic T cells. PLoS Pathog 11(11):e1005233. doi:10.1371/journal.ppat.1005233CrossRefPubMedPubMedCentralGoogle Scholar
  149. Smit TK, Brew BJ, Tourtellotte W, Morgello S, Gelman BB, Saksena NK (2004) Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment. J Virol 78(18):10133–10148. doi:10.1128/JVI.78.18.10133-10148.2004CrossRefPubMedPubMedCentralGoogle Scholar
  150. Spudich S, Lollo N, Liegler T, Deeks SG, Price RW (2006) Treatment benefit on cerebrospinal fluid HIV-1 levels in the setting of systemic virological suppression and failure. J Infect Dis 194(12):1686–1696. doi:10.1086/508750CrossRefPubMedGoogle Scholar
  151. Sung JA, Lam S, Garrido C, Archin N, Rooney CM, Bollard CM, Margolis DM (2015a) Expanded cytotoxic T-cell lymphocytes target the latent HIV reservoir. J Infect Dis 212(2):258–263. doi:10.1093/infdis/jiv022CrossRefPubMedPubMedCentralGoogle Scholar
  152. Sung JA, Pickeral J, Liu L, Stanfield-Oakley SA, Lam CY, Garrido C, Pollara J, LaBranche C, Bonsignori M, Moody MA, Yang Y, Parks R, Archin N, Allard B, Kirchherr J, Kuruc JD, Gay CL, Cohen MS, Ochsenbauer C, Soderberg K, Liao HX, Montefiori D, Moore P, Johnson S, Koenig S, Haynes BF, Nordstrom JL, Margolis DM, Ferrari G (2015b) Dual-Affinity Re-Targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells. J Clin Invest 125(11):4077–4090. doi:10.1172/JCI82314CrossRefPubMedPubMedCentralGoogle Scholar
  153. Takata H, Buranapraditkun S, Kessing C, Fletcher JL, Muir R, Tardif V, Cartwright P, Vandergeeten C, Bakeman W, Nichols CN, Pinyakorn S, Hansasuta P, Kroon E, Chalermchai T, O’Connell R, Kim J, Phanuphak N, Robb ML, Michael NL, Chomont N, Haddad EK, Ananworanich J, Trautmann L, Rv254/Search, the RVSSG (2017) Delayed differentiation of potent effector CD8+ T cells reducing viremia and reservoir seeding in acute HIV infection. Sci Transl Med 9 (377). doi:10.1126/scitranslmed.aag1809CrossRefGoogle Scholar
  154. Thompson M, Heath SL, Sweeton B, Williams K, Cunningham P, Keele BF, Sen S, Palmer BE, Chomont N, Xu Y, Basu R, Hellerstein MS, Kwa S, Robinson HL (2016) DNA/MVA vaccination of HIV-1 infected participants with viral suppression on antiretroviral therapy, followed by treatment interruption: elicitation of immune responses without control of re-emergent virus. PLoS ONE 11(10):e0163164. doi:10.1371/journal.pone.0163164CrossRefPubMedPubMedCentralGoogle Scholar
  155. Thornhill J, Inshaw J, Kaleebu P, Cooper D, Ramjee G, Schechter M, Tambussi G, Fox J, Samuel M, Miro JM, Weber J, Porter K, Fidler S (2016) Brief report: enhanced normalization of CD4/CD8 ratio with earlier antiretroviral therapy at primary HIV infection. J Acquir Immune Defic Syndr 73(1):69–73. doi:10.1097/QAI.0000000000001013CrossRefPubMedPubMedCentralGoogle Scholar
  156. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, Boulassel MR, Delwart E, Sepulveda H, Balderas RS, Routy JP, Haddad EK, Sekaly RP (2006) Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 12(10):1198–1202. doi:10.1038/nm1482CrossRefPubMedGoogle Scholar
  157. Tubiana R, Carcelain G, Vray M, Gourlain K, Dalban C, Chermak A, Rabian C, Vittecoq D, Simon A, Bouvet E, El Habib R, Costagliola D, Calvez V, Autran B, Katlama C, Vacciter Study g (2005) Therapeutic immunization with a human immunodeficiency virus (HIV) type 1-recombinant canarypox vaccine in chronically HIV-infected patients: the vacciter study (ANRS 094). Vaccine 23(34):4292–4301. doi:10.1016/j.vaccine.2005.04.013CrossRefGoogle Scholar
  158. Tung FY, Tung JK, Pallikkuth S, Pahwa S, Fischl MA (2016) A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy. Vaccine 34(19):2225–2232. doi:10.1016/j.vaccine.2016.03.021CrossRefPubMedGoogle Scholar
  159. UNAIDS (2016) Gobal AIDS update 2016. 2016
  160. Velu V, Titanji K, Zhu B, Husain S, Pladevega A, Lai L, Vanderford TH, Chennareddi L, Silvestri G, Freeman GJ, Ahmed R, Amara RR (2009) Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458(7235):206–210. doi:10.1038/nature07662CrossRefPubMedGoogle Scholar
  161. Vinuesa CG, Cyster JG (2011) How T cells earn the follicular rite of passage. Immunity 35(5):671–680. doi:10.1016/j.immuni.2011.11.001CrossRefPubMedGoogle Scholar
  162. Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM (2003) Antibody neutralization and escape by HIV-1. Nature 422(6929):307–312. doi:10.1038/nature01470CrossRefGoogle Scholar
  163. Williams JP, Hurst J, Stohr W, Robinson N, Brown H, Fisher M, Kinloch S, Cooper D, Schechter M, Tambussi G, Fidler S, Carrington M, Babiker A, Weber J, Koelsch KK, Kelleher AD, Phillips RE, Frater J, Investigators SP (2014) HIV-1 DNA predicts disease progression and post-treatment virological control. Elife 3:e03821. doi:10.7554/eLife.03821CrossRefPubMedPubMedCentralGoogle Scholar
  164. Wong JK, Yukl SA (2016) Tissue reservoirs of HIV. Curr Opin HIV AIDS 11(4):362–370. doi:10.1097/COH.0000000000000293CrossRefPubMedPubMedCentralGoogle Scholar
  165. Yamamoto T, Price DA, Casazza JP, Ferrari G, Nason M, Chattopadhyay PK, Roederer M, Gostick E, Katsikis PD, Douek DC, Haubrich R, Petrovas C, Koup RA (2011) Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood 117(18):4805–4815. doi:10.1182/blood-2010-11-317297CrossRefPubMedPubMedCentralGoogle Scholar
  166. Yu YJ, Atwal JK, Zhang Y, Tong RK, Wildsmith KR, Tan C, Bien-Ly N, Hersom M, Maloney JA, Meilandt WJ, Bumbaca D, Gadkar K, Hoyte K, Luk W, Lu Y, Ernst JA, Scearce-Levie K, Couch JA, Dennis MS, Watts RJ (2014) Therapeutic bispecific antibodies cross the blood-brain barrier in nonhuman primates. Sci Transl Med 6(261):261ra154. doi:10.1126/scitranslmed.3009835CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.U.S. Military HIV Research ProgramWalter Reed Army Institute of ResearchSilver SpringUSA
  2. 2.Henry M. Jackson Foundation for the Advancement of Military MedicineBethesdaUSA
  3. 3.Armed Forces Research Institute of Medical SciencesBangkokThailand
  4. 4.US Military HIV Research Program (MHRP)BethesdaUSA

Personalised recommendations